What else is new (pain)? DR ANDREW DAVIES

Transcription

1 What else is new (pain)? DR ANDREW DAVIES

2 Introduction

3 Outline Paracetamol for cancer pain IV paracetamol (for cancer pain) Vitamin D for cancer pain

4 Paracetamol for cancer pain

5 Paracetamol Mechanism of action: Uncertain Central action Multiple mechanism (? interlinked)

6 Paracetamol

7 Paracetamol Mechanism of action: Serotoninergic system* descending inhibitory pathways Eicosanoid system (prostaglandins) Opioid system Cannabinoid system Nitric oxide containing pathways

8 Paracetamol

9 Paracetamol We found no evidence that taking paracetamol together with a morphine-like drug was better than the morphinetype drug alone. Wiffen et al, 2017

10 Paracetamol Davies AN, Vriens J, Webber K, Mohammed K. An observational study of paracetamol (acetaminophen) deprescribing in patients with cancer pain receiving opioids for moderate-to-severe pain. Medycyna Paliatywna w Praktyce 2017; 11:

11 Paracetamol The aim of the current study was to obtain further data about the utility of paracetamol in patients receiving opioids for moderate-to-severe pain that are deemed to be well pain controlled (and specifically whether or not paracetamol can reasonably be omitted in this situation).

12 Paracetamol Inclusion criteria: > 18 yr Cancer diagnosis Regular opioid for moderate-to-severe pain for previous 7 days Regular oral paracetamol (i.e. 2 g / day) for previous 7 days Average pain intensity 4/10 for previous 24 hr

13 Paracetamol Exclusion criteria: Prognosis < 2 weeks Cognitive impairment Palliative radiotherapy in previous 4 weeks New oncology therapy in previous 4 weeks

14 Paracetamol Methods: Day 0 (face-to-face) Brief Pain Inventory- short form (BPI-SF) Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Discontinue paracetamol Day 2 (face-to-face or telephone) BPI-SF (pain scales)

15 Paracetamol Methods: Day 7 (face-to-face) BPI-SF Question since stopping your paracetamol do you feel your pain has got worse? Question since stopping your paracetamol do you feel you have had to use more breakthrough / rescue medication? Question do you want to restart your paracetamol?

16 Paracetamol Methods: If the patient wanted to restart paracetamol before the end of the study (and contacted the research team), they were asked to complete the pain scales on the BPI-SF before restarting the paracetamol and 48 hr after starting the paracetamol.

17 Paracetamol 44 patients randomised 40 patients completed 3 withdrawals (protocol violations) 1 death (progressive disease)

18 Paracetamol Characteristic Aetiology pain Cancer-related Cancer treatment related Unknown Pathophysiology of pain Nociceptive - somatic - visceral Neuropathic Mixed Number of patients (n = 44) 42 (96%) 1 (2%) 1 (2%) 39 (88.5%) - 27 (69%) -12 (31%) 0 (0%) 5 (11.5%)

19 Paracetamol Results: Patients that restarted paracetamol 18 patients (45%) 95% CI 30-60% 11 patients restarted before end of study (median 3 days)* 7 patients restarted at end of study *Pain scores available for 8 patients

20 Pain intensity (0-10 NRS) Paracetamol 10 Change in average pain intensity after re-starting paracetamol Patient 5 Patient 10 Patient 15 Patient 28 Patient 30 Patient 31 Patient 39 Patient 42 Average pain score on day of re-starting paracetamol Average pain score 2 days after re-starting paracetamol

21 Paracetamol Patient ID Worst pain day restarted Worst pain 2 days later Least pain day restarted Least pain 2 days later Patient Patient Patient Patient Patient Patient Patient Patient

22 Paracetamol Results: Patients that did not restart paracetamol 22 patients (55%) However 1 patient reported pain had got worse 2 patients reported using more rescue medication 1 patient reported both adverse effects

23 Paracetamol Results: Restarting paracetamol was associated with mixed pathophysiology (p = 0.013) Restarting paracetamol was not associated with demographics, aetiology of pain, baseline pain intensity scores, baseline opioid dosage

24 Paracetamol On the basis of these results (and those of Axelsson et al), we would recommend a trial of discontinuing paracetamol in all patients receiving opioids for moderate-to-severe pain who are adequately pain controlled.

25 Paracetamol The patients can be assured that there is approximately a one in two chance of not needing to restart paracetamol, and that if they do need to start the paracetamol, pain control can be regained within a very short period of time (i.e. less than 48 hours).

26 IV paracetamol (for cancer pain)

27 IV paracetamol For patients who can take an oral dosage form, not clear indication exists for preferential prescribing of IV acetaminophen. Jibril et al, 2015

28 IV paracetamol IV paracetamol can be used when administration PO or PR is not possible. PCF6, 2017

29 IV paracetamol Potential advantages: Non enteral route Pharmacokinetic profile - more predictable - avoidance first pass metabolism Pharmacodynamic profile - more predictable - faster onset of action (5-10 min for IV versus min for oral)

30 IV paracetamol Potential disadvantages: IV route - cannulation - adverse effects (e.g. phlebitis, infection) Health economics - direct costs - indirect costs

31 IV paracetamol Morphine co-administration significantly impacts the pharmacokinetics of oral but not intravenous paracetamol by reducing / delaying its absorption and substantially increasing the inter-individual pharmacokinetic variability. Raffa et al, 2018

32 IV paracetamol Predicted (solid blue) and observed (dashed red) pharmacokinetic profiles for a oral and b intravenous paracetamol. Subjects received Treatment A, i.e., 4 repeat doses of 1000 mg oral paracetamol (2 500 mg tablets) and an intravenous infusion of saline every 6 h (hours 0, 6, 12, and 18), and 2 infusions of intravenous morphine (0.125 mg/kg) at hours 6 and 12

33 Vitamin D for cancer pain

34 Vitamin C Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups. Carr et al, 2017

35 Vitamin D Vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency Helde-Frankling et al, 2017

36 Vitamin D

37 Vitamin D

38 Vitamin D

39 Vitamin D Analgesic effects: Analgesia variable Effect limited to patients with low vitamin D levels Effect related to correction of low vitamin D levels Anti-inflammatory (PGE 2) Modification nerve function

40 Vitamin D Bergman et al, 2015: Observational study 100 Swedish palliative care patients

41 Vitamin D Bergman et al, 2015: Patients with 25-hydroxyvitamin D < 50 nmol/l mean fentanyl dose 74 mcg / hr Patients with 25-hydroxyvitamin D > 50 nmol/l mean fentanyl dose 43 mcg / hr (p = 0.04)

42 Vitamin D

43 Vitamin D Bergman et al, 2015: Disease stage wasn t a confounding variable Higher age was a confounding variable - higher age was associated with higher 25-hydroxyvitamin D levels (in contrast to the general population), and lower fentanyl doses

44 Vitamin D Helde-Frankling et al, 2017: Interventional study (case control study) 78 Swedish palliative care patients - 39 cases (low 25-hydroxyvitamin D) - 39 matched controls (historical patients)

45 Vitamin D Helde-Frankling et al, 2017: Cases - > 18 yr - incurable cancer - expected survival > 1month - 25-hydroxyvitamin D < 75 nmol/l Vitamin D3 100 mcg/day

46 Vitamin D Helde-Frankling et al, 2017: Matched controls (Bergman et al, 2015) - sex - age (+/- 10 yr) - cancer type - 25-hydroxyvitamin D at baseline - survival time - number of days in study

47 Vitamin D

48 Vitamin D

49 Vitamin D

50 Vitamin D Helde-Frankling et al, 2017: 14 / 39 (36.0%) cases reduced fentanyl dose during study (7 patients stopped fentanyl) 1 / 39 (2.5%) controls reduced fentanyl dose during study 11 / 11 cases that were not receiving opioids at start of study remained opioid free at 1 month 6 / 12 controls that were not receiving opioids at start of study remained opioid free at 1 month

51 Vitamin D Helde-Frankling et al, 2017: No side effects were reported

52 Vitamin D

53 Conclusion

54 Conclusion the path of improvement which I have attempted imperfectly to indicate, would seem at present to lie far more in the better use of weapons long ready in our hand, than in the discovery of new. No one can pretend that the former have hitherto been employed in other than the most feeble and half-hearted fashion. Mr Herbert Snow